A DETAILED ANALYSIS OF THE KNODELL SCORE AND OTHER HISTOLOGIC PARAMETERS AS PREDICTORS OF RESPONSE TO INTERFERON THERAPY IN CHRONIC HEPATITIS-C

The Knodell score is inaccurate at predicting response to interferon a lpha (IFN-alpha) therapy in patients with hepatitis C. Our aim was to see if specific histologic parameters, including iron deposition in li ver biopsies, are better predictors of response to IFN-alpha than the total Knodell score. Thirty-five unselected patients were studied who had hepatitis C treated with IFN-alpha between 1990 and 1993, and pret reatment serum iron indices and liver needle biopsies performed. Biops ies were divided for light microscopy and quantitative iron determinat ion. H&E-stained slides were graded for components I, II, III, IV, and total Knodell score. Quantitative determinations were percentage of p ortal triads with inflammation, piecemeal necrosis, lymphoid aggregate s, and inflamed bile ducts; percentage of lobules with inflammation or acidophilic bodies; and percentage of triads with positive iron stain . Complete responders (CR) to IFN-alpha were defined by normalization of serum alanine aminotransferase (less than or equal to 40 IU/liter), and noncomplete responders (NCR) by partial or no response. Data were analyzed statistically. CR had <40% of triads positive for iron (P = 0.02) and lower serum ferritin (P = 0.05) and higher scores for lobula r necrosis (P = 0.04). The percentage of iron-positive triads correlat ed only with cirrhosis. Addition of cirrhosis to percentage of iron-po sitive triads did not improve the predictive power of the portal iron. CR and NCR did not differ with respect to total Knodell score or any of the other individual parameters except Knodell II. Conclusions: (a) Individual features of lobular necrosis and iron staining in portal t riads are better predictors of response to IFN-alpha than the total Kn odell score, (b) Portal iron staining alone may predict response to IF N-alpha in a high percentage of cases, with <40% of triads positive fo r iron being a positive predictor, (c) In patients with hepatitis C, l iver biopsy reports should include an assessment of lobular necrosis a nd the percentage of portal triads staining positive for iron.